Genentech, the Banner Alzheimer's Institute, and the National Institutes of Health are collaborating on the first-ever prevention trial in cognitively healthy individuals who are likely to develop Alzheimer's disease due to their genetic history.
The landmark trial is the first to assess the potential of a medicine to stop Alzheimer's before it starts and is the cornerstone of a new international collaborative, the Alzheimer's Prevention Initiative (API), formed to accelerate the evaluation of promising but unproven prevention therapies. The study will take place in Medellin, Colombia and will involve about 300 participants from local families that can be traced to a common descendant. The participants share a rare genetic mutation that typically triggers Alzheimer's symptoms around age 45. The study will also include a small number of individuals in the United States.
The study will involve crenezumab, a humanized monoclonal antibody, which is designed to bind to amyloid beta (Abeta), the main constituent of amyloid plaque in the brains of patients with Alzheimer's disease. Abeta is proposed to be causative in the development of the disease.
Why this trial is historic
- The trial will study patients before they show any symptoms of cognitive decline.
- The results may help determine if the amyloid hypothesis is correct.
- There is significant unmet medical need within this unique patient population.
Watch the interview series with Genentech's Executive Vice President of Research and Early Development, Richard Scheller.
This trial represents a significant shift in Alzheimer's disease research: from trying to reverse the damage to early prevention - which could be a decade or more before symptoms surface. If successful, this approach may allow earlier evaluation of promising medicines.
Because of the potential impact, Genentech has agreed to share data and findings with the entire research community after the trial is completed. This transparency could help further advance Alzheimer's research and encourage investigation of additional disease biomarkers. Furthermore, the findings may lead to similar studies in people at risk for the disease later in life.
The patient population in Colombia offers a truly unique opportunity because of its size, its shared genetic background and its long legacy with Alzheimer's. Indeed, no other location in the world offers a sufficiently large number of mutation carriers close to their age of potential disease onset for a study to determine whether a prevention treatment may work. This large, extended family has as many as 5,000 living members, many of whose own families have been devastated by the disease. The New York Times has covered the story of this family extensively.
See Related resources for links to the Times coverage.
The amyloid hypothesis proposes that the accumulation of toxic Abeta (a sticky protein also called beta amyloid peptide) leads to Alzheimer's. The Abeta protein is found in the plaques that accumulate in the brain and are the hallmark of Alzheimer's. By the time significant cognitive impairment starts to occur, patients already have a lot of amyloid plaque and their neurological function has begun to deteriorate.
"The question is," says Sean Bohen, senior vice president, Genentech Early Development, "if we intervene before cognitive function deteriorates, can we prevent the disease?"
The prevention trial may provide the most effective test to date of the amyloid hypothesis.
Two groups of patients, totaling as many as 324 people, will be involved in the study. About 300 live in the Antioquia region of Colombia, which includes the city of Medellín and is home to nearly 5,000 people who share the risk for a rare genetic mutation. This mutation, presenilin 1 (PSEN1), causes early-onset Alzheimer's in any individual who is a carrier. It was first identified in 1995.
Just over 100 participants will be mutation carriers who will receive the investigational treatment. Just over 100 participants will be mutation carriers who receive a placebo. Because most of those involved do not want to know their genetic status, just over 100 participants will be non-carriers who, since they have no risk for developing the disease at an early age, will only receive the placebo.
Participants will be 30 or older and within 15 years of the age when their parent's symptoms began (the age of clinical onset). Typically, mild cognitive impairment due to Alzheimer's begins in the Colombian families around 45.
In the United States, participants will be up to two-dozen individuals also at high risk for the disease because their family history indicates other, similar genetic mutations that are implicated in early-onset Alzheimer's.
People who are interested in supporting Alzheimer's prevention initiatives in the United States are encouraged to join the API's Alzheimer's Prevention Registry. The registry is a community of people interested in the possibility of participating in Alzheimer's prevention studies, now or in the future.
Watch the interview series with Genentech's Executive Vice President of Research and Early Development,Richard Scheller.
About Genentech's involvement in the Alzheimer's Prevention Trial to date and why we are grateful to the trial participants for this opportunity.
Why the patient population of the prevention trial is so unique and how Alzheimer's has had an impact on their lives.